angiopoietin

Angiopoietins are a family of secreted proteins that regulate angiogenesis and blood vessel maturation. Their effects are mediated mainly through the Tie2 receptor tyrosine kinase on endothelial cells, with Tie1 modulating signaling. The best characterized members are ANGPT1 and ANGPT2; ANGPT3 and ANGPT4 have been described in various species and are less well understood in humans.

Angiopoietin-1 (ANGPT1) binds Tie2 and acts as a receptor agonist, promoting endothelial quiescence, vessel stability, and barrier integrity. It supports mural cell recruitment and vessel maturation. Angiopoietin-2 (ANGPT2) is produced by endothelial cells and stored in Weibel-Palade bodies; upon stimulation it is released and can antagonize ANGPT1–Tie2 signaling, leading to vascular destabilization and remodeling. In the presence of vascular endothelial growth factor (VEGF), ANGPT2 facilitates sprouting and permeability; in other contexts it can act as a Tie2 agonist, illustrating its context-dependent effects.

Angiopoietin signaling engages downstream pathways such as PI3K–Akt and MAPK, promoting endothelial survival and barrier function when Tie2 is activated. ANGPT2 reduces Tie2 phosphorylation, shifting the balance toward remodeling and leakiness. The ANGPT–Tie2 axis interacts with VEGF signaling to coordinate angiogenesis and vascular stability and can influence inflammatory responses and vascular permeability.

Clinical relevance: Dysregulation of angiopoietin–Tie2 signaling is implicated in cancer, ocular neovascular diseases (such as age-related macular degeneration and diabetic retinopathy), sepsis, and other inflammatory conditions. ANGPT2 levels serve as a biomarker of endothelial dysfunction in some diseases. Therapeutic strategies target ANGPT2 signaling or use ANGPT1 mimetics; examples include ANGPT2 inhibitors and bispecific agents targeting ANGPT2 and VEGF, such as faricimab, developed for ocular angiopathies.